S304: SUTIMLIMAB, A COMPLEMENT C1S INHIBITOR, PROVIDES SUSTAINED IMPROVEMENTS IN PATIENT-REPORTED OUTCOMES IN PATIENTS WITH COLD AGGLUTININ DISEASE (CAD): 2 YEAR FOLLOW-UP FROM THE CARDINAL STUDY
Authors: A. Röth, C. M. Broome, W. Barcellini, T. Henrik Anderson Tvedt, Y. Miyakawa, S. D’Sa, D. Cella, F. Joly, J. Wang, T. Sourdille, F. Shafer, M. Wardęcki, I. C. Weitz
Journal: HemaSphere (2022)

Background: CAD is a rare chronic autoimmune hemolytic anemia characterized by classical complement pathway (CP)-mediated hemolysis, anemia, fatigue, and poor quality of life (QOL). Sutimlimab is a first-in-class humanized monoclonal antibody that selectively inhibits C1s of the C1 complex, preventing CP activation, while leaving the alternative and lectin pathways intact. One-year interim follow-up from the CARDINAL study (NCT03347396) have previously demonstrated continuous classical CP inhibition with sutimlimab resulted in rapid, sustained improvements in all patient-reported outcomes (PROs) measures evaluated. Aims: To report sutimlimab effect on PROs at 2 years, from the CARDINAL Part B extension. Methods: CARDINAL was a Phase 3, open-label, single-arm study with a 26-week treatment period (Part A) and a 2-year extension (Part B) after the last patient finishes Part A. Sutimlimab was administered through intravenous infusions on Days 0 and 7, followed by biweekly dosing. PRO data through Week 135, the last data recording within the 2-year Part B time period, are reported here. Efficacy endpoints included hemolytic markers and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) as a measure of QOL. Exploratory QOL endpoints included mean change from baseline in EuroQol 5-dimension 5-level (EQ-5D-5L) scores, 12-Item Short Form Health Survey (SF-12), Patient Global Impression of Change (PGIC) and Patient Global Impression of Fatigue Severity (PGIS). PRO measures were evaluated every 3 months and conducted in the following order: FACIT-Fatigue, PGIS, PGIC, SF-12 and EQ-5D-5L. Descriptive statistics, frequency, or percentage were used to analyze outcomes. Results: Overall, 24 patients enrolled and 22 finished Part A and entered Part B, with 19 (86.4%) patients completing Part B. The mean (SD) FACIT-Fatigue score at baseline was 32 (11) and improved by 7 (8) within 1 week of sutimlimab treatment; the mean change score from baseline remained ≥5 from Week 1 to Week 135 (minimum score of 38 (9) at Week 123, maximum score of 44 (5) at Week 7), consistent with a clinically meaningful improvement. Efficacy for the EQ-5D-5L visual analogue scale (VAS) was sustained over 2 years; the mean (SD) change from baseline in EQ-5D-5L visual analogue scale (VAS) score (n=15/22) at Week 135 was 17.1 (21.6) (Figure A). The majority of evaluable patients (n=13/15) indicated an improved disease state compared to baseline on the PGIC at Week 135. No or mild fatigue was reported in patients (80%, n=12/15) on completing PGIS at Week 135, compared with one-third at baseline (n=2/6). The mean increase in SF-12 physical and mental component scores (n=6/22) from baseline to Week 123 were 4.7 (6.9) and 3.8 (14.1) (Figure B), consistent with the clinically important changes of 3.9 and 2.8 respectively. Image:Summary/Conclusion: From this CARDINAL follow-up extension study, sutimlimab has shown to produce rapid and sustained improvements in FACIT-Fatigue and other PRO measures evaluated up to 2 years, demonstrating the continued meaningful impact of sutimlimab on patient QOL.